The development of new asymmetric catalysts for important synthetic reactions constitutes a significant and longstanding challenge. Aside from the relatively few transformations for which impressive enantioselectivities are obtainable using axially dissymmetric bisphosphines related to BINAP, there are numerous reactions in which only modest levels of enantioselection can be achieved with this class of ligands. Accordingly, there is presently a need for new, complementary classes of homochiral bisphosphines for asymmetric synthesis. Part I of this proposal is concerned with the design and synthesis of three new "families" of electronically and sterically differentiated bisphosphines in which the resident chirality exists at phosphorus. Subsequent to their preparation, these ligand classes will be systematically evaluated in asymmetric variations of Rh(I) catalyzed [4 + 2], [2+2+] and hydroboration reactions as well as alkene hydrocyanations catalyzed by Ni(0) and Pd(0). It is expected that the new homochiral ligands described herein will find numerous applications as enantioselective modifiers for other transformations catalyzed by transition metal complexes. Over the past three years, the Principal Investigator and his co-workers have been investigating several new annulation reactions mediated by group IV metal complexes. During the course of these studies, several novel coupling reactions were discovered which proceed with a high degree of chemo and stereoselectivity in many relatively simple model substrates. The focus of the studies described in Part II of this proposal will be the extension of our successes in this area to the group IV templated synthesis of several biologically active target structures. The molecules of interest not only possess a diverse spectrum of pharmacological activities but will also serve as operational models by which the crucial issues of stereo, regio, and chemocontrol associated with group IV mediated coupling processes can be evaluated. As a consequence of this investigation, the utility of these new reactions for effecting practical chemical synthesis of medicinally important compounds will be revealed.